The present invention relates generally to materials with molecular recognition properties. In particular, the present invention is directed toward a method of forming, using a molecular imprinting technique, metal oxide sol-gel materials with molecular recognition sites for use in sensor, separation, and catalysis operations.
Preparation of synthetic recognition, or receptor, sites for a variety of molecules in crosslinked organic polymers has previously been performed via the method of molecular imprinting. Molecular imprinting is a process for preparing materials that are selective for a particular compound (the imprint molecule) or set of related compounds. The imprinting molecule interacts with a complementary portion of a functional monomer, either covalently or by other interactions such as ionic, hydrophobic or hydrogen bonding, so that recognition sites for the imprinting molecule can be provided in the substrate material. The imprinting molecule is removed from the substrate to leave the recognition site that serves to interact with the imprinting molecule or some analogous molecule with similar physical/chemical characteristics. The material can then be used in sensor, separation or catalytic operations wherein the imprinting molecule can be targeted. The technique has also been referred to as host-guest polymerization or template polymerization.
Molecular imprinting creates specific recognition sites in materials, typically polymeric organic materials. For example, Mosbach (U.S. Pat. No. 5,110,883) describes the preparation of synthetic enzymes and synthetic antibodies by molecular imprinting techniques. Wulff (Wulff, G. Angew. Chem. Int. Ed. Engl. 1995, 34, 1812), prepared synthetic receptors for a variety of molecules in crosslinked organic polymers. Wulff describes investigations into a variety of binding polymers as well as siloxane monomers on different substrates, including silica gels and biopolymers. Materials prepared by Wulff et al. (Wulff, G.; Heide, B.; Helfmeier, G. J. Am. Chem. Soc. 1986, 108, 1089) employed diimine siloxane monomers that could be hydrolytically cleaved following attachment to the surface to yield bis-amine sites. Hydrolytic cleavage to break the covalent linkage between the template and functionalized surface created a receptor site composed of two aromatic amines spaced at a specific distance determined by the geometry of the dialdehyde template. Gels imprinted with diimines of isophthalaldehyde and (4,4'-dibenzaldehyde)methane showed good selectivities for their respective template molecules. Wulff (1995) also points out the potential uses of these materials in separations, such as chromatography and membrane operations, sensors, chemical reactions, and catalysis.
Yan et al. (U.S. Pat. No. 5,587,273) describe a molecular imprinting method using organic polymers, particularly allowing the manufacture of thin films on surfaces such as silicon wafers. This method has shown that some highly selective receptor sites can be built for complex molecules such as sugars, amino acids, peptides, nucleosides, among others, that operate in polar organic solvents. However, in aqueous solutions, imprinted polymers lose their affinity for substrates. Improvements in binding efficiencies may be achieved through a modification of the matrix or, alternatively, use of aqueous compatible materials such as metal oxide gels.
Molecular imprinting in metal oxide materials has been successfully achieved by other researchers including what is considered the first example of molecular imprinting by Dickey (Dickey, F. H, J. Phys. Chem. 1955, 59, 695), preparing silica gels in the presence of certain dyes. Dickey used a sol-gel method that created bulk phase material with dye molecules imbibed throughout the gel matrix. Washing of the gel removed the dye molecules leaving behind an imprinted site with recognition properties for the dye. Imprinted materials were produced using methyl, ethyl, propyl, and butyl orange dyes as templates and in each material the molecular recognition properties was greatest for the original template.
Glad et al., (Glad, M.; Norrlow, O.; Sellergren, B.; Siegbahn, N.; Mosbach, K. J. Chromatography 1985, 347, 11) used a surface imprinting technique to prepare receptor sites on commercially obtained silica gel. Glad et al. used a unique blend of phenyltriethoxysilane, N-2-aminoethyl-3-aminopropyltrimethoxysilane, and bis(2-hydroxy-ethyl)aminopropyltriethoxysilane monomers to heavily functionalize a silica surface. The gelation was performed in the presence of dye molecule Rhodanile blue or Safranine O at high temperature (85.degree. C.) and at low pH (2.5-3.0). The resultant materials exhibited good recognition properties for their original templates.
Recently, Pinel et al. used imprinted metal oxide sol-gels to separate enantiomers of menthol (Pinel, C.; Loisil, P.; Gallezot, P. Adv. Mater. 1997, 9, 582). The tetraethylorthosilicate sol-gel materials imprinted with (-)-menthol were catalyzed with acid, base, or fluoride and aged for two weeks prior to removal of template. Although the resultant gels gave no enantioselectivity in the binding of menthol, regioselectivity was observed with o-cresol having enhanced affinity over p-cresol, which is the opposite order of affinity on a control gel.
In addition to the use of these molecular recognition materials in separations operations, the materials can also be used in sensor and catalysis operations. For example, as sensor materials, molecular imprinted sol-gel materials offer ideal optically transmissive properties for optical detection schemes. Defense agencies are currently interested in remote and point sensors for the detection of chemical and biological weapons. Selective binding of phosphonate compounds at low concentration levels can allow the detection of nerve agents at levels below the threshold of human harm. The molecular imprinting technique of the present invention demonstrates the ability to build recognition sites for phosphonates compounds at the part per million (ppm) to tens of ppm level. For sensor applications, the selective and rapid detection of phosphate and phosphonate compounds, which include numerous biologically important signaling molecules as well as pesticides and chemical warfare agents, is dependent upon the development of efficient host-guest systems. The molecular imprinted sol-gel silicate materials of the present invention using guanidinium functionalized silanes offer high binding affinities (K.sub.a =10.sup.3 M.sup.-1) in aqueous solution for phosphates and phosphonates, which is one to two orders of magnitude higher than reported host-guest complexes (Dietrich, B.; Fyles, D. L.; Fyles, T. M.; Lehn, J.-M. Helv. Chim. Acta 1979, 62, 2763). The imprinted receptor sites show an improvement of about a factor of two higher in binding constants compared to randomly functionalized material.
Catalytic materials have been prepared in organic and silica materials through the molecular imprinting technique (see, for example, Wulff, 1995). The sol-gel process and post-modification methodology of the present invention allows access to uniquely functionalized receptor sites in inorganic and hybrid materials for catalysis for a variety of reactions. The aqueous compatibility of silica based materials allows access to catalytic reactions in aqueous solution, allowing chemical industries to perform reaction sequences in water and thereby reducing costs in solvents and environmental waste.
The ability to prepare robust inorganic materials with molecular recognition sites that function efficiently in both nonpolar and polar environments would offer a major improvement in the ability to generate separation materials for a larger variety of substrates and solvent systems. In particular, through the herein described sol-gel process and facile post modification of the materials, rapid tailoring can yield a large variety of substrate selective materials.